KEVZARA EFFICACY

COMBINATION THERAPY

demonstrated rapid, sustained, consistent clinical response

RELEVANT TRIALS: MOBILITY, TARGET

Pivotal Trial Study Designs

ACR20 clinical response was observed in MTX-IR and TNF-IR patients as early as 2 weeks in MOBILITY and as quickly as 4 weeks in TARGET, respectively, after the first dose.¹

ACR responses at week 24^2,3

ACR20 MOBILITY (MTX-IR) responses to treatment with KEVZARA® (sarilumab) after 24 weeks

ACR responseS at week 24^2,4

ACR20 TARGET (TNF-IR) responses to treatment with KEVZARA® (sarilumab) after 24 weeks

^*P<0.0001; ^†P<0.01.
^‡DMARD(s) in TARGET and MOBILITY include MTX, sulfasalazine, leflunomide, and/or hydroxychloroquine.

KEVZARA provided patients with uncontrolled RA
fast, lasting clinical improvement¹

ACR20 response sustained through week 52^1,2

ACR20 MOBILITY (MTX-IR) responses to treatment with KEVZARA® (sarilumab) through 52 weeks

ACR20 response sustained through week 24^1,2

ACR20 TARGET (TNF-IR) responses to treatment with KEVZARA® (sarilumab) through 24 weeks

^§P<0.0001, P value is for descriptive purposes only and is not adjusted for multiplicity.
^||P<0.0001.

MTX-IR=methotrexate inadequate response; TNF-IR=tumor necrosis factor inhibitor inadequate response or intolerant; ACR20=American College of Rheumatology 20% improvement criteria; MTX=methotrexate; q2w=once every 2 weeks; DMARDs=disease-modifying antirheumatic drugs.

Significant improvements in
HAQ-DI

∆HAQ-DI: MOBILITY ITT Population^1,2

Improvements in HAQ-DI MOBILITY (MTX-IR) at week 16 with KEVZARA® (sarilumab)

∆HAQ-DI: TARGET ITT Population^1,2

Improvements in HAQ-DI TARGET (TNF-IF) at week 12 with KEVZARA® (sarilumab)

OF MTX-IR PATIENTS MAINTAINED CLINICALLY MEANINGFUL IMPROVEMENT IN PHYSICAL FUNCTION THROUGH WEEK 52 WITH KEVZARA 200 mg + MTX^3*
Week 16: KEVZARA 200 mg + MTX: 57% (229/399) vs placebo + MTX: 42% (169/398);
Week 52: KEVZARA 200 mg + MTX: 48% (190/399) vs placebo + MTX: 26% (104/398)

*Minimal clinically important difference. HAQ-DI change from baseline ≥0.3 units.

HAQ-DI=Health Assessment Questionnaire-Disability Index; MTX-IR=methotrexate inadequate response; TNF-IR=tumor necrosis factor inhibitor inadequate response or intolerant; ITT=intent to treat; MTX=methotrexate; q2w=once every 2 weeks; DMARDs=disease-modifying antirheumatic drugs.

INHIBITION OF RADIOGRAPHIC PROGRESSION

56% OF MTX-IR PATIENTS HAD NO RADIOGRAPHIC PROGRESSION WITH KEVZARA AT 52 WEEKS vs 39% OF PATIENTS TREATED WITH PLACEBO^2*

MEAN CHANGE IN mTSS
AT WEEK 52^2,3

Studies looking at the effects of KEVZARA® (sarilumab) inhibition of joint damage through week 52

Participants saw 91% greater inhibition of joint damage progression with KEVZARA 200mg + MTX vs placebo + MTX2

greater inhibition of joint damage progression
with KEVZARA 200 mg + MTX vs placebo + MTX²

^*Defined as mean change from baseline in total Sharp score of ≤0.
^†Based on post hoc comparisons of mean change in mTSS per treatment group. Week 52 analysis employs linear extrapolation method to impute missing or post rescue data.²

MTX-IR=methotrexate inadequate response; mTSS=modified total Sharp score; MTX=methotrexate.

COMBINATION THERAPY
SAFETY DATA

Common adverse reactions in pre-rescue, placebo-controlled trials^1*

*Adverse reactions occurring in ≥2% of patients administered KEVZARA 200 mg or KEVZARA 150 mg + DMARD(s) and greater than observed in patients on placebo + DMARD(s).

Medically relevant AE occurring at an incidence of less than 2% in patients with RA treated with KEVZARA in controlled studies was oral herpes¹
Decrease in ANC was not associated with higher incidence of infections, including serious infections¹
In the long-term safety population, the overall rates of serious infections, GI perforations, neutrophil counts, platelet counts, and lipid parameters were consistent with what was observed in the placebo-controlled trials¹

DMARDs=disease-modifying antirheumatic drugs; ALT=alanine aminotransferase; ANC=absolute neutrophil count; GI=gastrointestinal.

Reference: 1. KEVZARA [prescribing information]. Bridgewater, NJ: Sanofi/Regeneron Pharmaceuticals, Inc.

VIEW SAFETY DATA

NEXT: LONG-TERM COMBINATION
THERAPY

References:

Data on file, Sanofi/Regeneron. Integrated summary. October 25, 2019.
KEVZARA [prescribing information]. Bridgewater, NJ: Sanofi/Regeneron Pharmaceuticals, Inc.
Genovese MC, Fleischmann R, Kivitz AJ, et al. Sarilumab plus methotrexate in patients with active rheumatoid arthritis and inadequate response to methotrexate: results of a phase III study. Arthritis Rheumatol. 2015;67(6):1424-1437.
Fleischmann R, Genovese M, Lin Y, et al. Long-term safety of sarilumab in rheumatoid arthritis: an integrated analysis with up to 7 years’ follow-up. Rheumatology (Oxford). 2019. doi:10.1093/rheumatology/kez265. [Epub ahead of print].

INDICATION

KEVZARA is indicated for treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs).

IMPORTANT SAFETY INFORMATION

WARNING: RISK OF SERIOUS INFECTIONS

Patients treated with KEVZARA are at increased risk for developing serious infections that may lead to hospitalization or death. Opportunistic infections have also been reported in patients receiving KEVZARA. Most patients who developed infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.

Avoid use of KEVZARA in patients with an active infection.

Reported infections include:

Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Patients should be tested for latent tuberculosis before KEVZARA use and during therapy. Treatment for latent infection should be initiated prior to KEVZARA use.
Invasive fungal infections, such as candidiasis, and pneumocystis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease.
Bacterial, viral and other infections due to opportunistic pathogens.

Closely monitor patients for signs and symptoms of infection during treatment with KEVZARA. If a serious infection develops, interrupt KEVZARA until the infection is controlled.

Consider the risks and benefits of treatment with KEVZARA prior to initiating therapy in patients with chronic or recurrent infection.

CONTRAINDICATION

Do not use KEVZARA in patients with known hypersensitivity to sarilumab or any of the inactive ingredients.

WARNINGS AND PRECAUTIONS

Infections. Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in patients receiving immunosuppressive agents for rheumatoid arthritis (RA). The most frequently observed serious infections with KEVZARA included pneumonia and cellulitis. Among opportunistic infections, TB, candidiasis, and pneumocystis were reported with KEVZARA.
- Hold treatment with KEVZARA if a patient develops a serious infection or an opportunistic infection.
- Patients with latent TB should be treated with standard antimycobacterial therapy before initiating KEVZARA. Consider anti-TB therapy prior to initiation of KEVZARA in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent TB but having risk factors for TB infection.
- Consider the risks and benefits of treatment prior to initiating KEVZARA in patients who have: chronic or recurrent infection, a history of serious or opportunistic infections, underlying conditions in addition to RA that may predispose them to infection, been exposed to TB, or lived in or traveled to areas of endemic TB or endemic mycoses.
- Viral reactivation has been reported with immunosuppressive biologic therapies. Cases of herpes zoster were observed in clinical studies with KEVZARA.
Laboratory Abnormalities. Treatment with KEVZARA was associated with decreases in absolute neutrophil counts (including neutropenia), and platelet counts; and increases in transaminase levels and lipid parameters (LDL, HDL cholesterol, and/or triglycerides). Increased frequency and magnitude of these elevations were observed when potentially hepatotoxic drugs (e.g., MTX) were used in combination with KEVZARA. Assess neutrophil count, platelet count, and ALT/AST levels prior to initiation with KEVZARA. Monitor these parameters 4 to 8 weeks after start of therapy and every 3 months thereafter. Assess lipid parameters 4 to 8 weeks after start of therapy, then at 6 month intervals.
Gastrointestinal Perforation. GI perforation risk may be increased with concurrent diverticulitis or concomitant use of NSAIDs or corticosteroids. Gastrointestinal perforations have been reported in clinical studies, primarily as complications of diverticulitis. Promptly evaluate patients presenting with new onset abdominal symptoms.
Immunosuppression. Treatment with immunosuppressants may result in an increased risk of malignancies. The impact of treatment with KEVZARA on the development of malignancies is not known but malignancies have been reported in clinical studies.
Hypersensitivity Reactions. Hypersensitivity reactions have been reported in association with KEVZARA. Hypersensitivity reactions that required treatment discontinuation were reported in 0.3% of patients in controlled RA trials. Injection site rash, rash, and urticaria were the most frequent hypersensitivity reactions. Advise patients to seek immediate medical attention if they experience any symptoms of a hypersensitivity reaction. If anaphylaxis or other hypersensitivity reaction occurs, stop administration of KEVZARA immediately. Do not administer KEVZARA to patients with known hypersensitivity to sarilumab.
Active Hepatic Disease and Hepatic Impairment. Treatment with KEVZARA is not recommended in patients with active hepatic disease or hepatic impairment, as treatment with KEVZARA was associated with transaminase elevations.
Live Vaccines. Avoid concurrent use of live vaccines during treatment with KEVZARA due to potentially increased risk of infections. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving KEVZARA.

ADVERSE REACTIONS

The most common serious adverse reactions were infections. The most frequently observed serious infections included pneumonia and cellulitis. The most common adverse reactions (occurred in at least 3% of patients treated with KEVZARA + DMARDs) are neutropenia, increased ALT, injection site erythema, upper respiratory infections, and urinary tract infections.

DRUG INTERACTIONS

Exercise caution when KEVZARA is co-administered with CYP substrates with a narrow therapeutic index (e.g. warfarin or theophylline), or with CYP3A4 substrates (e.g. oral contraceptives or statins) as there may be a reduction in exposure which may reduce the activity of the CYP3A4 substrate.
Elevated interleukin-6 (IL-6) concentration may down-regulate CYP activity such as in patients with RA and hence increase drug levels compared to subjects without RA. Blockade of IL-6 signaling by IL-6Rα antagonists such as KEVZARA might reverse the inhibitory effect of IL-6 and restore CYP activity, leading to altered drug concentrations.

USE IN SPECIFIC POPULATIONS

KEVZARA should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Because monoclonal antibodies could be excreted in small amounts in human milk, the benefits of breastfeeding and the potential adverse effects on the breastfed child should be considered along with the mother’s clinical need for KEVZARA.
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to KEVZARA during pregnancy. Physicians are encouraged to register patients and pregnant women are encouraged to register themselves by calling 1-877-311-8972.
Use caution when treating the elderly.

Advise patients to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

Please click here to see full Prescribing Information, including Boxed WARNING.